Long-term treatment with N-acetylcysteine, but not caloric restriction, protects mesenchymal stem cells of aged rats against tumor necrosis factor-induced death

The survival of mesenchymal stem cells (MSCs) to tumor necrosis factor alpha (TNFalpha) stimulation was evaluated after a long-term antioxidant treatment, or caloric restriction, in aged rats. MSCs were isolated from bone marrow of 30-month-old rats which orally received N-acetylcysteine in the last 18 months. The necrotic cell death-induced in vitro by TNFalpha, determined by trypan blue exclusion, was markedly attenuated in MSCs obtained from treated vs. control aged rats (percent mean+/-SEM: 10.9+/-2.17 vs. 17.8+/-0.53; p<0.05). Also, the proliferation rate of MSCs from control, but not N-acetylcysteine-treated, aged rats evaluated up to 2 weeks was significantly higher than that of MSCs from younger (4-month-old) rats. No significant effect was observed relative to the parameters investigated when the aged rats were previously subjected to a hypocaloric diet for 18 months. In conclusion, a prolonged supplementation with N-acetylcysteine in rats can increase resistance to necrotic death of MSCs and may also counteract an excessive rate of MSC proliferation.     

Skeletal muscle apoptosis, sarcopenia and frailty at old age

The loss of muscle mass and strength with aging, also referred to as sarcopenia of aging, is a highly prevalent condition among older adults and predicts several adverse outcomes, including disability, institutionalization and mortality. Although the exact mechanisms underlying sarcopenia are far to be unveiled, accumulating preclinical evidence suggests that an age-related acceleration of myocytes loss via apoptosis might represent a key mechanism driving the onset and progression of muscle loss. Furthermore, increased levels of apoptosis have also been reported in old rats undergoing acute muscle atrophy subsequent to muscle unloading, a condition that mimics the muscle loss observed during prolonged bed rest. Notably, preliminary evidence seems to confirm a causative role for apoptosis in age-related muscle loss in human subjects. Several signaling pathways of skeletal muscle apoptosis are currently under intense investigation, with a particular focus on the role played by mitochondria. Here, we will review the most recent evidence regarding various pathways of muscle apoptosis and their modulation by several interventions (caloric restriction, physical exercise, muscle unloading).     

A heritable cause of cleft lip and palate—Van der Woude syndrome caused by a novel IRF6 mutation. Review of the literature and of the differential diagnosis

Background  

Orofacial clefts are common congenital malformations usually characterized by a multifactorial etiology. These heterogeneous defects comprise cleft lip (CL), CL with cleft palate (CL/P), and cleft palate, sometimes observed in recognizable syndromes, with mendelian, chromosomal, or environmental pathogenesis. The Van der Woude syndrome is a mendelian CL/P, accounting for about 2% of all cases and caused by mutations in the interferon regulatory factor 6 (IRF6) gene, located on 1q32.2 chromosome.     

Estimation of bulky lymph nodes by power Doppler ultrasound scanning in patients with Hodgkin's lymphoma: a prospective study

The accuracy of standard methods in estimating bulky lesions requires validation. We used clinical/computed tomography (CT) evaluation and power Doppler ultrasound (US) to detect bulky disease in 137 consecutive Hodgkin's lymphoma patients, and analyzed the prognostic relevance of each method. Bulky disease was detected by clinical/CT evaluation in 47% of the patients and by power Doppler US in 20%. After treatment, at multivariate analysis power Doppler US-selected bulky disease was the parameter that best correlated with freedom from treatment failure (p<0.001). Power Doppler US, a readily available imaging technique, provides a better prognostic classification by detecting true bulky disease more accurately.     

Improvement of obstructive sleep apneas caused by hydrocephalus associated with Chiari malformation Type II following surgery

Chiari malformation (CM) is the downward herniation of the caudal part of the cerebellum and/or medulla oblongata into the spinal canal. It can alter several neurological functions, including respiratory control and upper airway motility, and can be the cause of sleep-disordered breathing (SDB). The authors describe a 6-year-old boy affected by CM Type II associated with myelomeningocele who showed symptoms indicative of severe airway obstruction during sleep. Polysomnography revealed severe obstructive sleep apnea syndrome (OSAS). Magnetic resonance imaging demonstrated herniation of the cerebellar tonsils and diffuse ventricular dilation with a large pseudocystic formation in the third ventricle. Surgical marsupialization of the cystic wall was performed, associated with ventriculocystostomy and endoscopic replacement of the ventricular catheter. Polysomnography repeated 2 months after surgery revealed a striking improvement in the sleep-related respiratory pattern. The pathogenesis of OSAS was probably referable to a combination of CM and elevated intracranial pressure. However, the striking improvement of symptoms after ventriculoatrial shunt placement suggested that hydrocephalus plays a major role in this condition. Assessment and effective treatment of SDB is crucial in the care of patients with CM.     

Dose-dense and high-dose chemotherapy plus rituximab with autologous stem cell transplantation for primary treatment of diffuse large B-cell lymphoma with a poor prognosis: a phase II multicenter study

Background

We investigated the addition of rituximab to dose-dense and high-dose chemotherapy with autologous stem cell transplantation in patients with untreated poor-prognosis diffuse large B-cell lymphoma.

Design and Methods

Ninety-four young patients (age, 18–60) with stage III–IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan (BEAM) with autologous stem cell transplantation.

Results

The complete response and toxic death rates were 82% and 5%, respectively. Failure-free survival and overall survival rates at 4 years were 73% and 80%, respectively. The outcomes of these patients were retrospectively compared to those of 41 patients with similar characteristics enrolled into a previous phase II trial of high-dose chemotherapy without rituximab. This historical group was treated with eight weekly infusions of methotrexate-doxorubicin-cyclophosphamide-vincristine-prednisone-bleomycin (MACOP-B), two courses of MAD and BEAM with autologous stem cell transplantation. The 4-year failure-free survival rates for the rituximab and historical groups were 73% versus 44%, respectively (p=0.001); the 4-year overall survival rates were 80% and 54%, respectively (p=0.002). A Cox’s multivariable model was applied to adjust the effect of treatment for unbalanced or important prognostic factors: failure and death risks were significantly reduced in the rituximab group compared to the historical group, with an adjusted hazard ratio of 0.44 (p=0.01) for failure-free survival and 0.46 (p=0.02) for overall survival.

Conclusions

These results suggest that the addition of rituximab to high-dose chemotherapy is effective and safe in diffuse large B-cell lymphoma with a poor-prognosis and such regimens need to be compared to dose-dense chemoimmunotherapy without autologous stem cell transplantation in randomized trials.     

Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study

Hypoxemia has been associated with low bone mineral density (BMD) in animal and human models. We assessed the association of haemoglobin levels with ultrasound-derived (UD) T score, Z score and the stiffness index in all 358 subjects aged 75+ living in Tuscania (Italy). Also, we searched for the haemoglobin cutoff levels that might best identify participants with osteoporosis. In the multivariable linear regression analysis, haemoglobin levels were associated among participants with the UD T score [β = 0.13; 95% confidence interval (CI) = 0.01–0.25; p = 0.030], Z score (β = 0.11; 95% CI = 0.01–0.22; p = 0.045) and stiffness index (β = 1.87; 95% CI = 0.51–3.21; p = 0.007) after adjusting for potential confounders. Haemoglobin levels <140 g/L in men and <130 g/L in women best predicted osteoporosis in linear discriminant analysis. Haemoglobin is independently associated with all UD-BMD parameters. Haemoglobin levels <140 g/L in men and 130 g/L in women might be adopted in clinical practice to identify older subjects in whom screening for osteoporosis might yield higher effectiveness.     

Neurophysiology and neurobiology of the musical experience

Music, a universal art form that exists in every culture around the world, is integral to a number of social and courtship activities, and is closely associated with other creative behaviours such as dancing. Recently, neuroimaging studies have allowed researchers to investigate the neural correlates of music processing and perception in the brain. Notably, musical stimuli have been shown to activate specific pathways in several brain areas associated with emotional behaviours, such as the insular and cingulate cortex, hypothalamus, hippocampus, amygdala, and prefrontal cortex. In addition, neurochemical studies have suggested that several biochemical mediators, such as endorphins, endocannabinoids, dopamine and nitric oxide, may play a role in the musical experience. A growing body of evidence also indicates that music therapy could be useful in the clinical management of numerous neurological and psychiatric disorders. Indeed, music therapy could be effective in patients with neurodegenerative disorders, such as Alzheimer's dementia and Parkinson?s disease, as well as in psychiatric illnesses, such as schizophrenia, depression, anxiety and autism spectrum disorders. Unfortunately, there is still a shortage of rigorous scientific data supporting the clinical application of music therapy, and there is thus a need to confirm and expand the preliminary findings regarding the potential and actual effectiveness of music therapy. This need should be addressed through prospective, randomized, controlled, single-blinded investigations of the short- and long-term effects of music therapy in diverse clinical conditions.     

A case of massive gastric necrosis in a young girl with Rett Syndrome

This is the unusual case of a 17-year-old girl affected by Rett Syndrome (RS) who suffered acute abdominal distension and constipation for a week. Laparotomy showed massive gastric dilatation, with total necrosis and perforation. Total gastrectomy and Y-Roux esophagojejunostomy were performed. We believe the clinical status was caused by the mechanism of air swallowing, present in our patient and typical in RS. In fact, as reported, massive air bloat may result in a decrease of the intramural blood flow with consequential ischemia of the gastric wall. We stress the importance of early detection of the gastroenterological symptoms in these patients, with timely positioning of nasogastric tube and gastrostomy, to prevent serious complications potentially life-threatening as massive gastric necrosis.